Primitive haematopoietic progenitors in the blood of patients with sickle cell disease appear to be endogenously mobilized

To investigate whether haematopoietic stem cells in patients with sickle ce ll (SS) disease might be altered, we examined the number and cycling status of 5-week long-term culture-initiating cells (LTC-ICs) and in vitro multil ineage colony-forming cells (CFCs) present in the blood of a large and clin ically diverse group of SS patients. The concentrations of both of these ce ll types per ml of blood varied over a wide range in individual patients, b ut, on average, were significantly elevated above normal values (similar to sevenfold and 15-fold respectively) and to an even greater extent than the lineage-restricted CFCs in the same samples. Wide variations in the concen tration of circulating progenitors, particularly the LTC-ICs, were also see n over time (in concert with changes in the white blood cell count) in SS p atients. [H-3]-Thymidine suicide assays showed most of the CFCs and LTC-ICs in SS blood to be quiescent like their counterparts in normal blood. Howev er, by comparison with historical data, the SS progenitors could be recruit ed into the cycle more quickly (i.e. within 2 vs. 3 d), thus showing the sa me kinetics of activation exhibited by 'mobilized' progenitors from patient s given chemotherapy and exogenous growth factors. Taken together, these fi ndings implicate previously documented increases in endogenous Steel factor , interleukin 3 and granulocyte-macrophage colony-stimulating factor levels in SS patients in the establishment of a chronically mobilized progenitor phenotype.